Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions
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AbstractPreliminary studies suggested that previous exposure to acetylcholine (ACh) exerts a delayed inhibition of subsequent contractions mediated by endothelium-derived contracting factor (EDCF). To confirm this long-term inhibitory effect of ACh and to determine whether nitric oxide ( NO) mediates the phenomenon, we suspended rings of spontaneously hypertensive rat (SHR) aortas in organ chambers for the recording of isometric force. The rings were incubated in the absence or presence of N-omega-nitro-L-arginine methyl ester (L-NAME; inhibitor of NO synthases) or 1H-[1,2,4] oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; inhibitor of soluble guanylyl cyclase) before exposure to increasing concentrations of ACh or sodium nitroprusside ( SNP) during contractions to phenylephrine. Thereafter, EDCF-mediated contractions to ACh or the calcium ionophore A-23187 were elicited. If the rings were preexposed to ACh or SNP, the subsequent ACh-induced EDCF-mediated contractions were reduced compared with those obtained in rings of the same arteries not previously exposed to either agent. ODQ did not affect the inhibition caused by preexposure to ACh but significantly reduced that caused by preexposure to SNP. Previous exposure to SNP reduced, whereas previous exposure to ACh did not affect, endothelium-dependent contractions to A-23187. Previous exposure to either ACh or SNP did not affect the contractions to the thromboxane mimetic U-46619. Thus ACh and SNP exert delayed inhibition of EDCF-mediated contractions via distinct pathways. The effect of ACh is NO independent and upstream of the increase in calcium concentration that triggers the release of EDCF. The effect of SNP is downstream of the calcium rise and is mainly NO dependent.
All Author(s) ListTang EHC, Feletou M, Huang Y, Man RYK, Vanhoutte PM
Journal nameAJP - Heart and Circulatory Physiology
Volume Number289
Issue Number6
PagesH2434 - H2440
LanguagesEnglish-United Kingdom
Keywordsendothelium-dependent contractions; endothelium-derived contracting factors; nitric oxide; spontaneously hypertensive rats
Web of Science Subject CategoriesCardiac & Cardiovascular Systems; CARDIAC & CARDIOVASCULAR SYSTEMS; Cardiovascular System & Cardiology; Peripheral Vascular Disease; PERIPHERAL VASCULAR DISEASE; Physiology; PHYSIOLOGY

Last updated on 2020-03-06 at 00:30